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    Clinical Trial Results:
    TRITON2: A Multicenter, Open-label Phase 2 Study of Rucaparib in Patients with Metastatic Castration-resistant Prostate Cancer Associated with Homologous Recombination Deficiency

    Summary
    EudraCT number
    		 2016-003162-13
    Trial protocol
    		 GB   IE   ES   BE   DK   FR   IT  
    Global end of trial date
    27 Jul 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    29 May 2022
    First version publication date
    29 May 2022
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CO-338-052
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02952534
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 IND : 129,840
    Sponsors
    Sponsor organisation name
    Clovis Oncology, Inc.
    Sponsor organisation address
    5500 Flatiron Parkway, Suite 100, Boulder, CO, United States, 80301
    Public contact
    Dr Lindsey Rolfe, Clovis Oncology, Inc., +44 1223 3645500, lrolfe@clovisoncology.com
    Scientific contact
    Dr Lindsey Rolfe, Clovis Oncology, Inc., +44 1223 3645500, lrolfe@clovisoncology.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Jul 2021
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Jul 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jul 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of rucaparib based on the response rate in metastatic castration-resistant prostate cancer (mCRPC) patients with homologous recombination deficiency (HRD) who progressed on AR-targeted therapy (abiraterone acetate, enzalutamide, apalutamide or investigational AR-targeted agent) and taxane-based chemotherapy in the castration resistant setting
    Protection of trial subjects
    Safety was assessed by evaluating hematology, biochemistry, urinalysis, vital signs, and changes in physical examination, and by monitoring the incidence, severity, and relationship of adverse events to rucaparib. Safety data was periodically reviewed by a Data Monitoring Committee (DMC). The DMC was comprised of study investigators and sponsor representatives.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Feb 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 29
    Country: Number of subjects enrolled
    United Kingdom: 15
    Country: Number of subjects enrolled
    Belgium: 10
    Country: Number of subjects enrolled
    Denmark: 5
    Country: Number of subjects enrolled
    France: 25
    Country: Number of subjects enrolled
    Germany: 20
    Country: Number of subjects enrolled
    Ireland: 12
    Country: Number of subjects enrolled
    Italy: 9
    Country: Number of subjects enrolled
    Israel: 7
    Country: Number of subjects enrolled
    United States: 113
    Country: Number of subjects enrolled
    Canada: 7
    Country: Number of subjects enrolled
    Australia: 25
    Worldwide total number of subjects
    277
    EEA total number of subjects
    110
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    65
    From 65 to 84 years
    205
    85 years and over
    7

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 277 patients were recruited from 102 sites across 12 countries.

    Pre-assignment
    Screening details
    		 After providing consent to participate, patients with a deleterious BRCA1/2, ATM, or other HRR gene mutation underwent Screening assessments within 28 days prior to the first dose of rucaparib.

    Period 1
    Period 1 title
    Overall Trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 BRCA Mutation
    Arm description
    		 Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All patients received open-label oral rucaparib 600 mg BID in continuous 28-day cycles. Patients were to take rucaparib with or without food.

    Arm title
    		 ATM Mutation
    Arm description
    		 Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All patients received open-label oral rucaparib 600 mg BID in continuous 28-day cycles. Patients were to take rucaparib with or without food.

    Arm title
    		 CDK12 Mutation
    Arm description
    		 Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All patients received open-label oral rucaparib 600 mg BID in continuous 28-day cycles. Patients were to take rucaparib with or without food.

    Arm title
    		 CHEK2 Mutation
    Arm description
    		 Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All patients received open-label oral rucaparib 600 mg BID in continuous 28-day cycles. Patients were to take rucaparib with or without food.

    Arm title
    		 Other Gene Mutation
    Arm description
    		 Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rucaparib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    All patients received open-label oral rucaparib 600 mg BID in continuous 28-day cycles. Patients were to take rucaparib with or without food.

    Number of subjects in period 1
    		BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Started
    172
    59
    14
    7
    25
    Completed
    172
    59
    14
    7
    25

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    BRCA Mutation
    Reporting group description
    		 Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.

    Reporting group title
    ATM Mutation
    Reporting group description
    		 Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.

    Reporting group title
    CDK12 Mutation
    Reporting group description
    		 Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.

    Reporting group title
    CHEK2 Mutation
    Reporting group description
    		 Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.

    Reporting group title
    Other Gene Mutation
    Reporting group description
    		 Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.

    Reporting group values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation Total
    Number of subjects
    		 172 59 14 7 25 277
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 39 8 9 3 6 65
        From 65-84 years
    		 128 51 5 2 19 205
        85 years and over
    		 5 0 0 2 0 7
    Age continuous
    Units: years
        median (full range (min-max))
    		 72 (49 to 88) 73 (51 to 84) 64 (49 to 79) 65 (60 to 86) 70 (57 to 83) -
    Gender categorical
    Units: Subjects
        Female
    		 0 0 0 0 0 0
        Male
    		 172 59 14 7 25 277
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0 0 0
        Asian
    		 3 0 0 1 1 5
        Native Hawaiian or Other Pacific Islander
    		 1 0 0 0 0 1
        Black or African American
    		 8 3 1 0 4 16
        White
    		 127 43 6 5 17 198
        More than one race
    		 0 0 0 0 0 0
        Unknown or Not Reported
    		 33 13 7 1 3 57

    End points

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    End points reporting groups
    Reporting group title
    BRCA Mutation
    Reporting group description
    		 Patients with a deleterious BRCA (breast cancer susceptibility gene) mutation detected in their tumor.

    Reporting group title
    ATM Mutation
    Reporting group description
    		 Patients with a deleterious ATM (ataxia telangiectasia mutated serine/threonine kinase) mutation detected in their tumor.

    Reporting group title
    CDK12 Mutation
    Reporting group description
    		 Patients with a deleterious CDK12 (Cyclin-dependent kinase 12) mutation detected in their tumor.

    Reporting group title
    CHEK2 Mutation
    Reporting group description
    		 Patients with a deleterious CHEK2 (Checkpoint Kinase 2) mutation detected in their tumor.

    Reporting group title
    Other Gene Mutation
    Reporting group description
    		 Patients with other deleterious HRR (homologous recombination repair) gene mutation detected in their tumor.

    Primary: Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR)

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    End point title
    		 Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Central Independent Radiology Review (IRR) [1]
    End point description
    The primary efficacy endpoint is confirmed radiographic ORR by central IRR. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
    End point type
    Primary
    End point timeframe
    Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: No formal statistical analyses are done for single arm studies. We present confidence intervals for ORR.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    81
    23
    8
    4
    17
    Units: Percentage of Patients
        number (confidence interval 95%)
    45.7 (34.6 to 57.1)
    0.0 (0.0 to 14.8)
    0.0 (0.0 to 36.9)
    0.0 (0.0 to 60.2)
    41.2 (18.4 to 67.1)
    No statistical analyses for this end point

    Secondary: Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV)

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    End point title
    		 Confirmed Objective Response Rate (ORR) by Gene in Patients With Measurable Disease at Baseline Per Investigator (INV)
    End point description
    A supportive efficacy endpoint is confirmed radiographic ORR by INV. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by mRECIST (modified Response Evaluation Criteria in Solid Tumors) v1.1/PCWG3 (Prostate Cancer Working Group 3) criteria. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation in the absence of confirmed progression in bone. CR is disappearance of all target and non-target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to<10 mm. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    87
    21
    9
    4
    17
    Units: Percentage of Patients
        number (confidence interval 95%)
    48.3 (37.4 to 59.2)
    9.5 (1.2 to 30.4)
    0.0 (0.0 to 33.6)
    25.0 (0.6 to 80.6)
    41.2 (18.4 to 67.1)
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR)

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    End point title
    		 Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Central Independent Radiology Review (IRR) [2]
    End point description
    A secondary efficacy endpoint is DOR by central IRR. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no patients with confirmed response by IRR in the ATM, CDK12 and CHEK2 arms.
    End point values
    		 BRCA Mutation Other Gene Mutation
    Number of subjects analysed
    37 [3]
    7 [4]
    Units: months
        median (confidence interval 95%)
    15.5 (6.4 to 36.2)
    22.1 (10.1 to 31.4)
    Notes
    [3] - Upper confidence interval not available due to insufficient number of patients so max 36.2 is noted.
    [4] - Upper confidence interval not available due to insufficient number of patients so max 31.4 is noted.
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator

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    End point title
    		 Duration of Response (DOR) by Gene in Patients With Confirmed Response Per Investigator [5]
    End point description
    A secondary efficacy endpoint is DOR as assessed by the investigator. The DOR is defined as the time from the date that a confirmed response per modified RECIST Version 1.1/PCWG3 is first reported to the time that progressive disease (PD) is first documented. Progressive disease is defined using RECIST v1.1, as at least a 20% increase in the sum of the diameters of target lesions, or an unequivocal increase in non-target lesions, or the appearance of new lesions. PCWG3 criteria is used to document evidence of disease progression in bone lesions.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
    Notes
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There were no patients with confirmed response by investigator in the CDK12 arm.
    End point values
    		 BRCA Mutation ATM Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    42
    2
    1 [6]
    7 [7]
    Units: Months
        median (confidence interval 95%)
    6.6 (5.6 to 11.6)
    7.5 (4.6 to 10.4)
    16.6 (16.6 to 16.6)
    18.4 (10.1 to 31.4)
    Notes
    [6] - There is only 1 responder in this group with DOR of 16.6 months.
    [7] - Upper confidence interval not available due to insufficient number of patients so max 31.4 is noted.
    No statistical analyses for this end point

    Secondary: Confirmed PSA Response (≥ 50% Decrease) by Gene as Assessed by Local Laboratory

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    End point title
    		 Confirmed PSA Response (≥ 50% Decrease) by Gene as Assessed by Local Laboratory
    End point description
    A secondary endpoint is confirmed PSA (prostate-specific antigen) response (≥ 50% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 50% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir in PSA.
    End point type
    Secondary
    End point timeframe
    PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    172
    59
    14
    7
    25
    Units: Percentage of Patients
        number (confidence interval 95%)
    53.5 (45.7 to 61.1)
    3.4 (0.4 to 11.7)
    7.1 (0.2 to 33.9)
    14.3 (0.4 to 57.9)
    36.0 (18.0 to 57.5)
    No statistical analyses for this end point

    Secondary: Confirmed PSA Response (≥ 90% Decrease) by Gene as Assessed by Local Laboratory

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    End point title
    		 Confirmed PSA Response (≥ 90% Decrease) by Gene as Assessed by Local Laboratory
    End point description
    A secondary endpoint is confirmed PSA (prostate-specific antigen) response (≥ 90% reduction) as assessed by local laboratory. Confirmed PSA response is analyzed for all patients who had PSA value at baseline and is defined as the percentage of patients having 2 consecutive PSA values (at least 3 weeks apart) that are at least 90% lower than baseline and that occur prior to PSA progression. PSA progression is defined as a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir in PSA.
    End point type
    Secondary
    End point timeframe
    PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    172
    59
    14
    7
    25
    Units: Percentage of Patients
        number (confidence interval 95%)
    19.8 (14.1 to 26.5)
    0 (0 to 0)
    0 (0 to 0)
    14.3 (0.4 to 57.9)
    16.0 (4.5 to 36.1)
    No statistical analyses for this end point

    Secondary: Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR)

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    End point title
    		 Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Central Independent Radiology Review (IRR)
    End point description
    A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by IRR. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression adjudicated by IRR using the PCWG3 guidelines for bone disease and modified RECIST Version1.1 for soft tissue disease.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    172
    59
    14
    7 [8]
    25
    Units: months
        median (confidence interval 95%)
    10.7 (8.7 to 13.2)
    5.3 (3.7 to 8.9)
    3.7 (1.9 to 8.3)
    9.4 (2.1 to 24.8)
    11.6 (5.1 to 25.3)
    Notes
    [8] - Upper confidence interval not available due to insufficient number of patients so max 24.8 is noted.
    No statistical analyses for this end point

    Secondary: Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator

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    End point title
    		 Radiologic Progression-free Survival (rPFS) by Gene in All Patients Per Investigator
    End point description
    A secondary efficacy endpoint is Radiologic Progression-free Survival (rPFS) assessed by Investigator. rPFS is defined as the time from first dose of rucaparib to the date of first objective evidence of radiographic progression (soft tissue or bone lesion) or death due to any cause, whichever occurs first, plus 1 day. Radiographic disease progression includes confirmed bone disease progression and soft tissue disease progression using the PCWG3 guidelines for bone disease and modified RECIST Version 1.1 for soft tissue disease.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    172
    59
    14
    7
    25
    Units: months
        median (confidence interval 95%)
    9.6 (8.2 to 11.2)
    7.8 (4.2 to 10.6)
    3.7 (1.9 to 8.1)
    3.5 (2.1 to 11.2)
    11.6 (5.8 to 22.3)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) by Gene

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    End point title
    		 Overall Survival (OS) by Gene
    End point description
    A secondary efficacy endpoint is Overall Survival (OS). OS is defined as the date from first dose of rucaparib to the date of death due to any cause, +1 day.
    End point type
    Secondary
    End point timeframe
    From date of first dose until event, loss to follow-up, withdrawal of consent, or study closure
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    172
    59
    14
    7
    25 [9]
    Units: months
        median (confidence interval 95%)
    17.2 (14.8 to 20.0)
    14.6 (12.0 to 19.0)
    13.9 (6.8 to 18.6)
    11.1 (3.5 to 26.7)
    11.6 (8.9 to 34.9)
    Notes
    [9] - Upper confidence interval not available due to insufficient number of patients so max 34.9 is noted.
    No statistical analyses for this end point

    Secondary: Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR)

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    End point title
    		 Clinical Benefit Rate (CBR) by Gene Per Central Independent Radiology Review (IRR)
    End point description
    A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by IRR. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    172
    59
    14
    7
    25
    Units: participants
        6 months
    100
    10
    2
    2
    13
        12 months
    36
    3
    0
    1
    6
    No statistical analyses for this end point

    Secondary: Clinical Benefit Rate (CBR) by Gene Per Investigator

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    End point title
    		 Clinical Benefit Rate (CBR) by Gene Per Investigator
    End point description
    A secondary efficacy endpoint is Clinical Benefit Rate (CBR) assessed by Investigator. CBR is defined as the number of patients without radiographic progression (defined by modified RECIST Version 1.1/ PCWG3 criteria) who were continuing with study drug treatment through the given time interval divided by the number of patients who had the given amount of follow-up. Clinical benefit rates are summarized at 6 and 12 months.
    End point type
    Secondary
    End point timeframe
    Assessments every 8 weeks from study day 1 for the first 24 weeks, and then every 12 weeks until disease progression, death, or initiation of subsequent treatment. Total follow-up was up to approximately 3 years.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    172
    59
    14
    7
    25
    Units: participants
        6 months
    103
    17
    3
    2
    14
        12 months
    39
    6
    1
    1
    6
    No statistical analyses for this end point

    Secondary: Time to PSA Progression by Gene

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    End point title
    		 Time to PSA Progression by Gene
    End point description
    A secondary efficacy endpoint is time to PSA progression. Time to PSA progression is defined as the time from first dose of rucaparib to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline if there was no PSA decline after baseline) in PSA was measured, plus 1 day. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later (unless the PSA progression occurred at the last recorded PSA assessment). If confirmed, the date used for time of PSA progression is the earlier of the 2 PSA dates.
    End point type
    Secondary
    End point timeframe
    PSA assessments were done at baseline, Week 5, Week 9, every 4 weeks thereafter, and at Treatment Discontinuation. Total follow-up was up to approximately 39 months.
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    172
    59
    14
    7 [10]
    25
    Units: months
        median (confidence interval 95%)
    6.5 (5.7 to 7.5)
    3.1 (2.8 to 3.7)
    3.5 (2.8 to 4.6)
    5.6 (2.8 to 24.9)
    5.3 (3.0 to 9.1)
    Notes
    [10] - Upper confidence interval not available due to insufficient number of patients so max 24.9 is noted.
    No statistical analyses for this end point

    Secondary: Steady State Trough (Cmin) Level Rucaparib Concentrations

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    End point title
    		 Steady State Trough (Cmin) Level Rucaparib Concentrations
    End point description
    Trough (Cmin) concentrations of rucaparib are summarized for all patients with at least one PK sample collected. The absolute values of rucaparib plasma concentration at each time point are presented by gene.
    End point type
    Secondary
    End point timeframe
    Participants were assessed at Study Day 29, Day 57, Day 85 and Day 113
    End point values
    		 BRCA Mutation ATM Mutation CDK12 Mutation CHEK2 Mutation Other Gene Mutation
    Number of subjects analysed
    101 [11]
    51 [12]
    14 [13]
    5 [14]
    13 [15]
    Units: ng/mL
    median (standard deviation)
        Day 29
    1539.565 ( 966.2604 )
    1605.002 ( 856.2478 )
    1639.357 ( 1428.5691 )
    1286.998 ( 1138.2119 )
    1189.845 ( 748.3045 )
        Day 57
    1578.353 ( 1057.8049 )
    1600.380 ( 1198.3899 )
    1405.167 ( 806.4642 )
    1841.667 ( 2106.3362 )
    1792.499 ( 1672.7732 )
        Day 85
    1308.704 ( 693.6717 )
    1505.400 ( 802.0812 )
    1699.700 ( 991.9922 )
    815.500 ( 557.9073 )
    2255.889 ( 1831.9626 )
        Day 113
    1533.690 ( 889.6130 )
    1515.300 ( 1291.8497 )
    1520.700 ( 884.1374 )
    728.000 ( 469.5189 )
    1433.875 ( 637.4535 )
    Notes
    [11] - Day 29 = 101 pts, Day 57 = 85, Day 85 = 71, Day 113 = 60
    [12] - Day 29 = 48 pts, Day 57 = 38, Day 85 = 30, Day 113 = 22
    [13] - Day 29 = 14 pts, Day 57 = 12, Day 85 = 10, Day 113 = 10
    [14] - Day 29 = 5 pts, Day 57 = 3, Day 85 = 2, Day 113 = 2
    [15] - Day 29 = 13 pts, Day 57 = 11, Day 85 = 9, Day 113 = 8
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from date of first dose of study drug until 28 days after last dose of study drug, approximately 4.5 years.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.0
    Reporting groups
    Reporting group title
    All patients
    Reporting group description
    		 All patients received open-label oral rucaparib 600 mg BID (twice a day) in continuous 28-day cycles.

    Serious adverse events
    		 All patients
    Total subjects affected by serious adverse events
         subjects affected / exposed
    96 / 277 (34.66%)
         number of deaths (all causes)
    8
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma pancreas
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bladder cancer
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Malignant neoplasm progression
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Vascular disorders
    Embolism
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Fatigue
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pain
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative respiratory failure
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract stoma complication
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    3 / 277 (1.08%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    3 / 277 (1.08%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronary artery occlusion
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Torsade de pointes
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Ventricular tachycardia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Cerebellar infarction
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Cerebrovascular accident
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dizziness
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Dysarthria
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Presyncope
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sacral radiculopathy
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Seizure
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Syncope
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    14 / 277 (5.05%)
         occurrences causally related to treatment / all
    17 / 19
         deaths causally related to treatment / all
    0 / 0
    Anaemia of malignant disease
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Aplastic anaemia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pancytopenia
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 277 (1.08%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Intestinal ischaemia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Mechanical ileus
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Oesophagitis
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rectal haemorrhage
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 277 (1.08%)
         occurrences causally related to treatment / all
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    7 / 277 (2.53%)
         occurrences causally related to treatment / all
    3 / 7
         deaths causally related to treatment / all
    0 / 0
    Haematuria
         subjects affected / exposed
    6 / 277 (2.17%)
         occurrences causally related to treatment / all
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary retention
         subjects affected / exposed
    3 / 277 (1.08%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Muscular weakness
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pain in extremity
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Pathological fracture
         subjects affected / exposed
    5 / 277 (1.81%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 0
    Spinal pain
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Abscess oral
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Device related infection
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Fournier's gangrene
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemophilus infection
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infective exacerbation of chronic obstructive airways disease
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Legionella infection
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Paraspinal abscess
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonia
         subjects affected / exposed
    6 / 277 (2.17%)
         occurrences causally related to treatment / all
    0 / 6
         deaths causally related to treatment / all
    0 / 1
    Pneumonia legionella
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Pneumonia staphylococcal
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    4 / 277 (1.44%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    4 / 277 (1.44%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Urosepsis
         subjects affected / exposed
    4 / 277 (1.44%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Electrolyte imbalance
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Failure to thrive
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 277 (0.36%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    2 / 277 (0.72%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 All patients
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    274 / 277 (98.92%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    20 / 277 (7.22%)
         occurrences all number
    26
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    50 / 277 (18.05%)
         occurrences all number
    100
    Fatigue
         subjects affected / exposed
    131 / 277 (47.29%)
         occurrences all number
    249
    Oedema peripheral
         subjects affected / exposed
    50 / 277 (18.05%)
         occurrences all number
    58
    Pyrexia
         subjects affected / exposed
    16 / 277 (5.78%)
         occurrences all number
    23
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    33 / 277 (11.91%)
         occurrences all number
    36
    Dyspnoea
         subjects affected / exposed
    40 / 277 (14.44%)
         occurrences all number
    66
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    18 / 277 (6.50%)
         occurrences all number
    20
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    72 / 277 (25.99%)
         occurrences all number
    120
    Aspartate aminotransferase increased
         subjects affected / exposed
    71 / 277 (25.63%)
         occurrences all number
    106
    Blood alkaline phosphatase increased
         subjects affected / exposed
    18 / 277 (6.50%)
         occurrences all number
    30
    Blood creatinine increased
         subjects affected / exposed
    51 / 277 (18.41%)
         occurrences all number
    76
    Platelet count decreased
         subjects affected / exposed
    32 / 277 (11.55%)
         occurrences all number
    112
    Weight decreased
         subjects affected / exposed
    45 / 277 (16.25%)
         occurrences all number
    64
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    19 / 277 (6.86%)
         occurrences all number
    31
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    54 / 277 (19.49%)
         occurrences all number
    71
    Dysgeusia
         subjects affected / exposed
    32 / 277 (11.55%)
         occurrences all number
    41
    Headache
         subjects affected / exposed
    28 / 277 (10.11%)
         occurrences all number
    30
    Neuropathy peripheral
         subjects affected / exposed
    14 / 277 (5.05%)
         occurrences all number
    17
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    130 / 277 (46.93%)
         occurrences all number
    460
    Neutropenia
         subjects affected / exposed
    20 / 277 (7.22%)
         occurrences all number
    63
    Thrombocytopenia
         subjects affected / exposed
    33 / 277 (11.91%)
         occurrences all number
    92
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    17 / 277 (6.14%)
         occurrences all number
    19
    Constipation
         subjects affected / exposed
    76 / 277 (27.44%)
         occurrences all number
    107
    Diarrhoea
         subjects affected / exposed
    66 / 277 (23.83%)
         occurrences all number
    100
    Dyspepsia
         subjects affected / exposed
    18 / 277 (6.50%)
         occurrences all number
    23
    Nausea
         subjects affected / exposed
    140 / 277 (50.54%)
         occurrences all number
    231
    Vomiting
         subjects affected / exposed
    70 / 277 (25.27%)
         occurrences all number
    114
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    18 / 277 (6.50%)
         occurrences all number
    20
    Photosensitivity reaction
         subjects affected / exposed
    19 / 277 (6.86%)
         occurrences all number
    22
    Rash
         subjects affected / exposed
    22 / 277 (7.94%)
         occurrences all number
    27
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    24 / 277 (8.66%)
         occurrences all number
    46
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    44 / 277 (15.88%)
         occurrences all number
    65
    Back pain
         subjects affected / exposed
    51 / 277 (18.41%)
         occurrences all number
    74
    Bone pain
         subjects affected / exposed
    18 / 277 (6.50%)
         occurrences all number
    26
    Muscular weakness
         subjects affected / exposed
    17 / 277 (6.14%)
         occurrences all number
    21
    Musculoskeletal chest pain
         subjects affected / exposed
    14 / 277 (5.05%)
         occurrences all number
    17
    Musculoskeletal pain
         subjects affected / exposed
    34 / 277 (12.27%)
         occurrences all number
    41
    Myalgia
         subjects affected / exposed
    14 / 277 (5.05%)
         occurrences all number
    16
    Pain in extremity
         subjects affected / exposed
    33 / 277 (11.91%)
         occurrences all number
    49
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    20 / 277 (7.22%)
         occurrences all number
    24
    Urinary tract infection
         subjects affected / exposed
    39 / 277 (14.08%)
         occurrences all number
    60
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    96 / 277 (34.66%)
         occurrences all number
    137
    Dehydration
         subjects affected / exposed
    15 / 277 (5.42%)
         occurrences all number
    22
    Hypocalcaemia
         subjects affected / exposed
    21 / 277 (7.58%)
         occurrences all number
    35
    Hypophosphataemia
         subjects affected / exposed
    27 / 277 (9.75%)
         occurrences all number
    44

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Oct 2016
    Added monitoring and management guidelines for anemia and MDS/AML because these events were reported with rucaparib as with other PARP inhibitors. Added language describing when treatment beyond radiographic progression may be appropriate. Added study drug interruption and discontinuation criteria for cases of DILI per Hy’s Law. Clarified that bone scans were to be performed at each time of disease assessment, in addition to CT/MRI, to follow PCWG3 guidelines.
    12 Dec 2017
    Updated the inclusion criterion for renal function. Updated inclusion criterion 11 to avoid exposure of the partners of male patients to semen containing rucaparib. Included and emphasized specific warnings and protection measures regarding photosensitivity. Updated precautions related to concomitant medications, particularly for CYP drugs.
    12 Jun 2018
    Agents that target the AR pathway that are given for metastatic hormone-sensitive prostate cancer and for non-metastatic CRPC were now considered to meet prior AR-directed therapy requirements. Removed collection of blood samples for CTC analysis as exploratory analysis indicated an overall lack of feasibility.
    24 Aug 2020
    The sponsor designated pneumonitis as an AESI in response to a request from the US FDA. Updated the interval from 6 months to 3 months after the last dose of study drug for which men must use contraceptive measures or abstinence or refrain from donating semen.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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